Wain J, Pham V B, Ha V, Nguyen N M, To S D, Walsh A L, Parry C M, Hasserjian R P, HoHo V A, Tran T H, Farrar J, White N J, Day N P
Wellcome Trust Clinical Research Unit, Centre for Tropical Diseases, Ho Chi Minh City, Vietnam.
J Clin Microbiol. 2001 Apr;39(4):1571-6. doi: 10.1128/JCM.39.4.1571-1576.2001.
Enteric fever is the only bacterial infection of humans for which bone marrow examination is routinely recommended. A prospective study of the concentrations of bacteria in the bone marrow and their relationship to clinical features was conducted with 120 Vietnamese patients with suspected enteric fever, of whom 89 had confirmed typhoid fever. Ninety-three percent of the Salmonella enterica serovar Typhi samples isolated were resistant to ampicillin, chloramphenicol, and co-trimoxazole. For 81 patients with uncomplicated typhoid and satisfactory bone marrow aspirates, the number of serovar Typhi CFU in bone marrow aspirates was a median value of 9 (interquartile range [IQR], 1 to 85; range, 0.1 to 1,580) compared to 0.3 (IQR, 0.1 to 10; range, 0.1 to 399) CFU/ml in simultaneously sampled blood. The ratio of individual blood counts to bone marrow counts was 10 (IQR, 2.3 to 97.5). The number of bacteria in blood but not bone marrow was correlated inversely with the duration of preceding fever. Thus, with increasing duration of illness the ratio of bone marrow-to-blood bacterial concentrations increased; the median ratio was 4.8 (IQR, 1 to 27.5) during the first week compared with 158 (IQR, 60 to 397) during the third week. After lysing the host cells, the median ratio of viable bone marrow to blood increased, reflecting the higher concentration of intracellular serovar Typhi in the bone marrow. Effective antibiotic pretreatment had a significantly greater effect in reducing blood counts compared to bone marrow counts (P < 0.001). Thus, bacteria in the bone marrow of typhoid patients are less affected by antibiotic treatment than bacteria in the blood. The numbers of bacteria in bone marrow correlated negatively with the white blood cell (R = -0.3, P = 0.006) and platelet counts (R = -0.32, P = 0.01) and positively with fever clearance time after treatment (R = 0.4, P < 0.001). The bacterial load in bone marrow therefore may reflect the clinical course of the infection, and high levels may suppress neutrophil proliferation.
肠热症是唯一一种常规推荐进行骨髓检查的人类细菌感染疾病。对120名疑似肠热症的越南患者进行了一项关于骨髓中细菌浓度及其与临床特征关系的前瞻性研究,其中89人确诊为伤寒热。分离出的肠炎沙门氏菌伤寒血清型样本中有93%对氨苄青霉素、氯霉素和复方新诺明耐药。对于81例无并发症伤寒且骨髓穿刺结果满意的患者,骨髓穿刺液中伤寒血清型CFU数量的中位数为9(四分位间距[IQR],1至85;范围,0.1至1580),而同时采集的血液中CFU/ml为0.3(IQR,0.1至10;范围,0.1至399)。个体血液计数与骨髓计数的比值为10(IQR,2.3至97.5)。血液中而非骨髓中的细菌数量与之前发热的持续时间呈负相关。因此,随着病程延长,骨髓与血液中细菌浓度的比值增加;第一周时中位数比值为4.8(IQR,1至27.5),而第三周时为158(IQR,60至397)。裂解宿主细胞后,存活的骨髓与血液的中位数比值增加,反映出骨髓中细胞内伤寒血清型的浓度更高。有效的抗生素预处理在降低血液计数方面的效果明显大于骨髓计数(P < 0.001)。因此,伤寒患者骨髓中的细菌比血液中的细菌受抗生素治疗的影响更小。骨髓中的细菌数量与白细胞计数(R = -0.3,P = 0.006)和血小板计数(R = -0.32,P = 0.01)呈负相关,与治疗后发热消退时间呈正相关(R = 0.4,P < 0.001)。因此,骨髓中的细菌负荷可能反映感染的临床进程,高水平可能抑制中性粒细胞增殖。